LAUSR

Chronic hepatitis B virus (HBV) infection is a global public health problem. The gut microbiota has been linked to pathogenesis of liver diseases induced by chronic HBV infection. In this study, a recombinant adeno-associated virus serotype 8 (rAAV8) mediated persistent HBV infection mouse model was established, and entecavir (ETV) treatment significantly decreased the HBV DNA load both in serum and liver. The comparison of gut microbiota composition of rAAV8-HBV infected mice and ETV treated mice with healthy controls was carried out using 16S rDNA sequencing analysis of the cecal content samples. The intestinal microbiota alpha diversity of rAAV8-HBV infected mice decreased, and significantly restored after 4 weeks of ETV therapy. Blautia and Clostridium sensu stricto decreased significantly in rAAV8-HBV infected mice and correlated negatively with both HBsAg and HBeAg level. On the contrary, Butyricicoccus and Prevotellaceae NK3B31 group exhibited positive correlation with HBsAg and HBeAg. Furthermore, we observed that Akkermansia, a known gut barrier-protecting bacterium, decreased significantly in rAAV8-HBV infected mice and restored to the level of that in healthy controls after ETV therapy, while the abundance of Akkermansia was negatively correlated with HBV DNA load both in serum and in liver. Taken together, the results showed that dysbiosis of gut microbiota developed in the persistent HBV infected mice and effectively reversed by ETV treatment, shedding light on the mechanisms of gut microbiota on HBV persistent infection and antiviral therapy.